Multiple myeloma is an incurable tumor with modest treatment options. It is an attractive model to study immune tumor interactions, as both the primary tumor and the infiltrating immune T cells can be readily isolated without the need for ex vivo culture. Our preliminary studies show that transformation of preneoplastic gammopathy to clinical myeloma is associated with a progressive decline in tumor reactive innate and adaptive immune effector function in the tumor bed. We have also found that dendritic cells (DCs) can acquire antigen from autologous tumor cells and lead to the generation of tumor specific killer T cells. Here, we test the hypothesis that injection of tumor loaded dendritic cells will lead to enhancement of antitumor immunity, which can be assessed at the level of the tumor microenvironment. Our long term goal is to optimize the ability of DCs to boost anti-tumor immunity in patients. Herein, we propose to 1) optimize the presentation of tumor antigens from autologous myeloma cells by dendritic cells; 2) examine the feasibility and tolerability of injection of tumor loaded DCs in patients with persistent / high risk myeloma; 3) assess immune responses to tumor specific vaccination and compare responses in blood versus tumor bed; and 4) assess changes in the expression of interferon-y responsive genes in tumor cells following vaccination. These studies may not only provide the basis of a novel approach to boost anti-tumor immunity in myeloma, but also yield insights into the role of tumor microenvironment in assessing the efficacy of anti-tumor vaccination.